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姜黄素对原代瘢痕疙瘩成纤维细胞中 TGF-β1/SMAD 通路及细胞外基质产生的抑制作用:其在瘢痕疙瘩化学预防中的潜在治疗用途。

Suppression of TGF-β1/SMAD pathway and extracellular matrix production in primary keloid fibroblasts by curcuminoids: its potential therapeutic use in the chemoprevention of keloid.

机构信息

Graduate Institute of Medical Science and Innovative Research Center of Medicine, College of Health Sciences, Chang Jung Christian University, No. 396. Sec. 1, Changrong Rd., Gueiren Township, Tainan 71101, Taiwan.

出版信息

Arch Dermatol Res. 2010 Dec;302(10):717-24. doi: 10.1007/s00403-010-1075-y. Epub 2010 Aug 18.

DOI:10.1007/s00403-010-1075-y
PMID:20717830
Abstract

Keloid is a fibrotic disease characterized by abnormal accumulation of extracellular matrix (ECM) in the dermis. It is a late spreading skin overgrowth and may be considered a plastic surgeon's nightmare. In nature, curcuminoid is composed of curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (bDMC). Curcuminoids have been found to inhibit fibrosis. However, their role in the synthesis of ECM in the keloid fibroblasts (KFs) has remained unclear. In this series of studies, a total of seven primary KFs cultures were used as the KFs model for investigating the inhibitory effect of curcuminoids on the expression of ECM and TGF-β1. A sensitive and reproducible HPLC method was developed to provide a quantitative analysis on the cellular uptake of curcuminoids onto the KF cells. The level of ECM in the primary KFs was elevated. The elevation of ECM and TGF-β1/p-SMAD-2 level was substantially blocked by the cellular uptake of curcumin in a dose-dependent manner in all the seven primary KFs. The results have led to the conclusion that the excessive production of ECM in the KF cells could be blocked and/or rapidly decreased by curcumin.

摘要

瘢痕疙瘩是一种纤维性疾病,其特征是真皮中细胞外基质(ECM)的异常积聚。它是一种晚期扩散性皮肤过度生长,可能被认为是整形外科医生的噩梦。在自然界中,姜黄素由姜黄素、脱甲氧基姜黄素(DMC)和双脱甲氧基姜黄素(bDMC)组成。已经发现姜黄素类能够抑制纤维化。然而,它们在瘢痕成纤维细胞(KFs)中 ECM 合成中的作用仍不清楚。在这一系列研究中,共使用了 7 种原代 KF 培养物作为 KF 模型,以研究姜黄素类对 ECM 和 TGF-β1 表达的抑制作用。开发了一种灵敏且可重现的 HPLC 方法,对 KF 细胞摄取姜黄素类的情况进行定量分析。原代 KF 中的 ECM 水平升高。在所有 7 种原代 KF 中,姜黄素的细胞摄取以剂量依赖性方式显著阻止了 ECM 和 TGF-β1/p-SMAD-2 水平的升高。研究结果表明,姜黄素可以阻断和/或迅速减少 KF 细胞中 ECM 的过度产生。

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